5-sulfamyl-3-substituted-1,3,4-thiadiazol-2-ones



S-SULFAMYL-S-SUBSTITUTED-l,3,4-THIADIAZOL- Richard William Young,Riverside, and Melinda Jane Muller, Stamford, Conn., assignors toAmerican Cyanamid Company, New York, N. Y., a corporation of Maine NDrawing. Application August 13, 1956 Serial No. 603,844

13 Claims. (Cl. 260-3063) This invention relates to new organiccompounds and more particularly is concerned with novel -sulfamyl-3-substituted-1,3,4-thiadiazol-2-ones which may be represented by thefollowing general formula ONNls l'SOzNH:

wherein R has the same meaning as above. The nitrosimino compounds maybe prepared by nitrosating an appropriate 5-imino-4-substituted Al,3,4-thiadiazoline-2- sulfonamide with nitrous acid at a temperatureranging from about 0 C. to 30 C. The compounds so prepared have beenfound to be useful natriuretic agents, that is, agents which enhance theexcretion of sodium in the urine without necessarily changing to normalvolume of urine excreted.

The S-imino compounds, in turn, are prepared by the acid hydrolysis ofS-acylimino-4-substituted-A -1,3,4- thiadiazoline-Z-sulfonamides whichare more particularly described and claimed in the copending applicationof Young, Wood and Vaughan, Serial No. 492,297, filed March 4, 1955, nowPatent No. 2,783,241, and the copending application of Young and Muller,Serial No. 560,866, filed January 23, 1956, now Patent No. 2,783,239.

We have now discovered that effective naturetic agents may be preparedby pyrolyzing the S-nitrosimino compounds of our aforesaid copendingapplication filed concurrently herewith. This is preferably accomplishedby pyrolyzing the nitrosimino compound in the presence of a suitablenon-hydroxylated organic solvent, such as dimethylformamide. forexample, by heating to reflux temperatures, that is temperatures of theorder of 50 C. to 200 C. Suitable inert organic solvents, in addition todimethylformamide, are toluene, chloroform, carbon tetrachloride.diuxane, benzene, chlorobenzene, xylene, etc. If desired. the processmay also be carried out in the absence of solvents simply by heating thecompounds to the melting point.

rates Patent ice The process by which the novel compounds of thisinvention may be prepared is illustrated schematically below using5-nitrosimino-4-methyl-A -1,3,4-thiadiazoline- 2-sulfonamide as anexample of a suitable 4-substituted nitrosimino compound anddimethylformamide as an example of a suitable organic solvent.

The invention will be described in greater detail in conjunction withthe following specific examples in which the parts are by weight unlessotherwise specified.

Example 1 One part of 5-nitrosimino-4-methyl-A-1,3,4-thiadiazoline-Z-sulfonamid is pyrolyzed by adding the sampleslowly to 10 parts of refluxing dimethylformamide. Each addition resultsin the rapid evolution of gas. The dark solution is refluxed until itbecomes decolorized and gas The reaction mixture is concentrated todryness under water pump vacuum and the resulting solid is slurried inchloroform to give 0.47 part (53%), of a product having a melting pointof 130-133 C. The product is precipitated twice from methyl isobutylketone by the addition of petroleum ether and 0.1 part (11%), M. P.131133 C., of 5-sulfamyl-3-methyl-1,3,4-

. thiadiazol-Z-one is recovered.

Example 2 5 nitrosimino4-phenyl-A -l,3,4-thiadiazoline-2-sulfonamide ispyrolyzed in refluxing dimethylformamide by the procedure of Example 1.5-sulfamyl-3-phenyl-1,3,4- thiadiazol-Z-one is obtained.

Example 3 5 nitrosimino-4-(m-tolyl)-A -1,3,4-thiadiazoline-2-su1-fonamide is pyrolyzed in refluxing toluene by the procedure ofExample 1. 5-sulfamyl-3-(m-tolyl)-1,3,4-thiadiazol-Z-one is produced.

Example 4 5 nitrosimino 4 (p-chlorophenyl)-A-l,3,4-thiadiazoline-Z-sulfonamide is pyrolyzed in reflux xylene by theprocedure of Example 1.5-sulfamyl-3-(p-chlorophenyl)-1,3,4-thiadiazol-2-one is produced.

Example 5 The procedure of Example 1 is repeated with the sole exceptionthat 5-nitrosimino-4-benzyl A 1,3,4 thiadiazoline-Z-sulfonamide is usedinstead of the S-nitrosimino- 4-methyl compound of Example 1.5-sulfamyl-3-benzyl- 1,3,4-thiadiazol-2-one is obtained.

Example 6 The procedure of Example 1 is followed except that 5-nitrosimino-4-(p-acetamidophenyl)-A -l,3,4-thiadiazoline- 2-sulfonamideis used. 5-sulfamyl-3-(p-acetamidophenyl)- 1,3,4-thiadiazol-2-one isproduced.

Example 7 Example 8 The procedure of Example 1 is repeated except thatno solvent is used and the nitrosimino compound is heated to the meltingpoint. The same product as in Example 1 is obtained.

7 3 We fclaim: 1. -sulfamyl-3 substituted 1,3,4-thiadiazol 2 Ones of theformula;

R-N-N wherein R is a member'selected from the groupr consisting of loweralkyl, phenyl, halo-substituted phenyl,-

nitro-substituted phenyl, amide-substituted.phenyl, loweralkoxy-substituted phenyl, lower alkyl-substituted phenyl, andphenyl-lower-alkyl radicals.

2. 5-sulfamyl-3-methyl-1,3,4-thiadiazol-2-one:'

3. 5-sulfamyl-3-phenyl-l,3,4-thiadiazol-2-one.

4. 5-sulfamyl-3 -benzy1- 1 ,3 ,4-thiadiazol-2-one.

6. 5 sulfamyl 3-(p chlorophenyn-1,3,4-thiadiazo1-2- one.

7. Themethod of preparing 5-sulfarnyl-3-substituted-1,3,4-thiadiazo1-2-ones of the formula:

wherein .R is amember selected from the group consisting'of loweralkyl,phenyl, halo-substituted phenyl, nitro-substituted phenyl,amide-substituted phenyl,.lower aikoxy-substituted phenyl, loweralkyl-substituted phenyl,. and. phenyl-lower-alkyl radicals.whichcomprises heatingv a compoundof the formula:.

wherein R has the same meaning as above in the presence of anon-hydroxylated organic solvent underreflux -con-. ditions.

8. The method of preparing'5-sulfamyl-3methyl-1,3,4- thiadiazol-Z-onewhich comprises -heating 5-nitrosimino- 4-methy1-A-1,3,4-thiadiazoline-Z-sulfonarnide in the presence of dimethylformamideunder reflux conditions.

9. The method of preparing 5-sulfarnyl-3-phenyl1,3,4- thiadiazol-Z-onewhich comprises heating 5-nitrosimino-.

4-phenyl- A -l,3,4-thiadiazoline-2-sulfonamide in the presence ofdimethylformamide underreflux conditions.

10. The method of preparing 5-sulfamyl 3-.benzyl l,3,4

thiadiazol-Z-one which comprises heating S-nitrosiminowhereinRJisnamembenselected from the group consisting of lower. alkyl; phenyl,halo-substituted phenyl,

nitro-substituted Iphenyl; amido-substituted phenyl,loweralkyl-substituted phenyl, and phenyl-lower-alkyl radicals, whichcomprises.heating a-compound of theformular oNN Lsl SOiNfiz" wherein R'hasthe 'same meanin'g'as' above at temperames'i of from'50 C. to 200'C. in the 'ab'sen'ce ofa"solvent.

No references "cited.

1. 5-SULFAMYL-3-SUBSTITUED-1,3,4-THIADIAZOL - 2 - ONES OF THE FORMULA: